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. 1977 Oct;60(4):885–899. doi: 10.1172/JCI108843

Evidence for Cardiomyopathy in Familial Diabetes Mellitus

Timothy J Regan 1,2,3, Michael M Lyons 1,2,3, S Sultan Ahmed 1,2,3, Gilbert E Levinson 1,2,3, Henry A Oldewurtel 1,2,3, Mehmood R Ahmad 1,2,3, Bunyad Haider 1,2,3
PMCID: PMC372437  PMID: 893679

Abstract

Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age.

Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia.

Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.

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Selected References

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  1. Ahmed S. S., Jaferi G. A., Narang R. M., Regan T. J. Preclinical abnormality of left ventricular function in diabetes mellitus. Am Heart J. 1975 Feb;89(2):153–158. doi: 10.1016/0002-8703(75)90039-3. [DOI] [PubMed] [Google Scholar]
  2. Alavaikko M., Elfving R., Hirvonen J., Järvi J. Triglycerides, cholesterol, and phospholipids in normal heart papillary muscle and in patients suffering from diabetes, cholelithiasis, hypertension, and coronary atheroma. J Clin Pathol. 1973 Apr;26(4):285–293. doi: 10.1136/jcp.26.4.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrade Z. A., Teixeira A. R. Changes in the coronary vasculature in endomyocardial fibrosis and their possible significance. Am Heart J. 1973 Aug;86(2):152–158. doi: 10.1016/0002-8703(73)90238-x. [DOI] [PubMed] [Google Scholar]
  4. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  5. Bemiller C. R., Pepine C. J., Rogers A. K. Long-term observations in patients with angina and normal coronary arteriograms. Circulation. 1973 Jan;47(1):36–43. doi: 10.1161/01.cir.47.1.36. [DOI] [PubMed] [Google Scholar]
  6. Brady A. J. Active state in cardiac muscle. Physiol Rev. 1968 Jul;48(3):570–600. doi: 10.1152/physrev.1968.48.3.570. [DOI] [PubMed] [Google Scholar]
  7. Brown A. K., Epstein E. J., Coulshed N., Clarke J. M., Doukas N. G. Haemodynamic changes after angiocardiography. Br Heart J. 1969 Mar;31(2):233–245. doi: 10.1136/hrt.31.2.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bruschke A. V., Proudfit W. L., Sones F. M., Jr Clinical course of patients with normal, and slightly or moderately abnormal coronary arteriograms. A follow-up study on 500 patients. Circulation. 1973 May;47(5):936–945. doi: 10.1161/01.cir.47.5.936. [DOI] [PubMed] [Google Scholar]
  9. Buja L. M., Khoi N. B., Roberts W. C. Clinically significant cardiac amyloidosis. Clinicopathologic findings in 15 patients. Am J Cardiol. 1970 Oct;26(4):394–405. doi: 10.1016/0002-9149(70)90736-8. [DOI] [PubMed] [Google Scholar]
  10. Camerini-Davalos R. A., Oppermann W., Velasco C., Cole H. S. Abnormalities at the stage of chemical asymptomatic diabetes. Metabolism. 1973 Feb;22(2):219–228. doi: 10.1016/0026-0495(73)90164-9. [DOI] [PubMed] [Google Scholar]
  11. Chew C., Ziady G. M., Raphael M. J., Oakley C. M. The functional defect in amyloid heart disease. The "stiff heart" syndrome. Am J Cardiol. 1975 Oct 6;36(4):438–444. doi: 10.1016/0002-9149(75)90891-7. [DOI] [PubMed] [Google Scholar]
  12. Dwyer E. M., Jr Left ventricular pressure-volume alterations and regional disorders of contraction during myocardial ischemia induced by atrial pacing. Circulation. 1970 Dec;42(6):1111–1122. doi: 10.1161/01.cir.42.6.1111. [DOI] [PubMed] [Google Scholar]
  13. Dyer A. R., Stamler J., Berkson D. M., Lindberg H. A. Relationship of relative weight and body mass index to 14-year mortality in the Chicago Peoples Gas Company study. J Chronic Dis. 1975 Feb;28(2):109–123. doi: 10.1016/0021-9681(75)90067-3. [DOI] [PubMed] [Google Scholar]
  14. Ettinger P. O., Oldewurtel H. A., Dzindzio B., Sethi V., Regan T. J. Glucose intolerance in nonischemic cardiac disease. Role of cardiac output and adrenergic function. Circulation. 1971 Jun;43(6):809–823. doi: 10.1161/01.cir.43.6.809. [DOI] [PubMed] [Google Scholar]
  15. Falsetti H. L., Mates R. E., Grant C., Greene D. G., Bunnell I. L. Left ventricular wall stress calculated from one-plane cineangiography. Circ Res. 1970 Jan;26(1):71–83. doi: 10.1161/01.res.26.1.71. [DOI] [PubMed] [Google Scholar]
  16. Falsetti H. L., Mates R. E., Greene D. G., Bunnell I. L. Vmax as an index of contractile state in man. Circulation. 1971 Apr;43(4):467–479. doi: 10.1161/01.cir.43.4.467. [DOI] [PubMed] [Google Scholar]
  17. Farrer-Brown G., Tarbit M. H., Somers K., Hutt M. S. Microvascular study of hearts with endomyocardial fibrosis. Br Heart J. 1972 Dec;34(12):1250–1262. doi: 10.1136/hrt.34.12.1250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fletcher R. F. Lipids of human myocardium. Lipids. 1972 Nov;7(11):728–732. doi: 10.1007/BF02533122. [DOI] [PubMed] [Google Scholar]
  19. Frank M. J., Cundey P. E., Jr, Crews T. L., Lewis W. J., 3rd Comparison of left ventricular volumes by single-plane cineangiography and by indicator dilution. J Lab Clin Med. 1971 Apr;77(4):580–593. [PubMed] [Google Scholar]
  20. Fredrickson D. S., Levy R. I., Lees R. S. Fat transport in lipoproteins--an integrated approach to mechanisms and disorders. N Engl J Med. 1967 Jan 19;276(3):148–contd. doi: 10.1056/NEJM196701192760305. [DOI] [PubMed] [Google Scholar]
  21. GREENGARD P. Determination of intermediary metabolites by enzymic fluorimetry. Nature. 1956 Sep 22;178(4534):632–634. doi: 10.1038/178632a0. [DOI] [PubMed] [Google Scholar]
  22. Garcia M., McNamara P., Gordon T., Kannel W. B. Cardiovascular complications in diabetics. Adv Metab Disord. 1973;2(Suppl):493–499. doi: 10.1016/b978-0-12-027362-1.50057-1. [DOI] [PubMed] [Google Scholar]
  23. Greene D. G., Carlisle R., Grant C., Bunnell I. L. Estimation of left ventricular volume by one-plane cineangiography. Circulation. 1967 Jan;35(1):61–69. doi: 10.1161/01.cir.35.1.61. [DOI] [PubMed] [Google Scholar]
  24. Grossman W., McLaurin L. P., Stefadouros M. A. Left ventricular stiffness associated with chronic pressure and volume overloads in man. Circ Res. 1974 Nov;35(5):793–800. doi: 10.1161/01.res.35.5.793. [DOI] [PubMed] [Google Scholar]
  25. Hamby R. I., Zoneraich S., Sherman L. Diabetic cardiomyopathy. JAMA. 1974 Sep 23;229(13):1749–1754. [PubMed] [Google Scholar]
  26. Herman M. V., Heinle R. A., Klein M. D., Gorlin R. Localized disorders in myocardial contraction. Asynergy and its role in congestive heart failure. N Engl J Med. 1967 Aug 3;277(5):222–232. doi: 10.1056/NEJM196708032770502. [DOI] [PubMed] [Google Scholar]
  27. Hugenholtz P. G., Wagner H. R., Sandler H. The in vivo determination of left ventricular volume. Comparison of the fiberoptic-indicator dilution and the angiocardiographic methods. Circulation. 1968 Apr;37(4):489–508. doi: 10.1161/01.cir.37.4.489. [DOI] [PubMed] [Google Scholar]
  28. Kannel W. B., Hjortland M., Castelli W. P. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29–34. doi: 10.1016/0002-9149(74)90089-7. [DOI] [PubMed] [Google Scholar]
  29. Kemp H. G., Jr, Vokonas P. S., Cohn P. F., Gorlin R. The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience. Am J Med. 1973 Jun;54(6):735–742. doi: 10.1016/0002-9343(73)90060-0. [DOI] [PubMed] [Google Scholar]
  30. Kennedy J. W., Reichenbach D. D., Baxley W. A., Dodge H. T. Left ventricular mass. A comparison of angiocardiographic measurements with autopsy weight. Am J Cardiol. 1967 Feb;19(2):221–223. doi: 10.1016/0002-9149(67)90536-x. [DOI] [PubMed] [Google Scholar]
  31. Keroes J., Rapaport E. Ventricular volume measurement in the awake dog using implanted thermistor beads. J Appl Physiol. 1972 Mar;32(3):404–408. doi: 10.1152/jappl.1972.32.3.404. [DOI] [PubMed] [Google Scholar]
  32. Kessler I. I. Mortality experience of diabetic patients. A twenty-six-year follow-up study. Am J Med. 1971 Dec;51(6):715–724. doi: 10.1016/0002-9343(71)90299-3. [DOI] [PubMed] [Google Scholar]
  33. Kjeldsen H., Hansen A. P., Lundbaek K. Twenty-four-hour serum growth hormone levels in maturity-onset diabetics. Diabetes. 1975 Nov;24(11):977–982. doi: 10.2337/diab.24.11.977. [DOI] [PubMed] [Google Scholar]
  34. Klein L., Butcher D. L., Sudilovsky O., Kikkawa R., Miller M. Quantification of collagen in renal glomeruli isolated from human nondiabetic and diabetic kidneys. Diabetes. 1975 Dec;24(12):1057–1065. doi: 10.2337/diab.24.12.1057. [DOI] [PubMed] [Google Scholar]
  35. LEVINE J. B., ZAK B. AUTOMATED DETERMINATION OF SERUM TOTAL CHOLESTEROL. Clin Chim Acta. 1964 Oct;10:381–384. doi: 10.1016/0009-8981(64)90073-7. [DOI] [PubMed] [Google Scholar]
  36. LOWRY O. H., PASSONNEAU J. V., HASSELBERGER F. X., SCHULZ D. W. EFFECT OF ISCHEMIA ON KNOWN SUBSTRATES AND COFACTORS OF THE GLYCOLYTIC PATHWAY IN BRAIN. J Biol Chem. 1964 Jan;239:18–30. [PubMed] [Google Scholar]
  37. Ledet T. Histological and histochemical changes in the coronary arteries of old diabetic patients. Diabetologia. 1968 Nov;4(5):268–272. doi: 10.1007/BF01309899. [DOI] [PubMed] [Google Scholar]
  38. Levinson G. E., Frank M. J., Nadimi M., Braunstein M. Studies of cardiopulmonary blood volume. Measurement of left ventricular volume by dye dilution. Circulation. 1967 Jun;35(6):1038–1048. doi: 10.1161/01.cir.35.6.1038. [DOI] [PubMed] [Google Scholar]
  39. Maron B. J., Ferrans V. J., Roberts W. C. Myocardial ultrastructure in patients with chronic aortic valve disease. Am J Cardiol. 1975 May;35(5):725–739. doi: 10.1016/0002-9149(75)90065-x. [DOI] [PubMed] [Google Scholar]
  40. Maseri A., Enson Y. Mixing in the right ventricle and pulmonary artery in man: evaluation of ventricular volume measurements from indicator washout curves. J Clin Invest. 1968 Apr;47(4):848–859. doi: 10.1172/JCI105778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. McCans J. L., Parker J. O. Left ventricular pressure-volume relationships during myocardial ischemia in man. Circulation. 1973 Oct;48(4):775–785. doi: 10.1161/01.cir.48.4.775. [DOI] [PubMed] [Google Scholar]
  42. Melada G. A., Goldman R. H., Luetscher J. A., Zager P. G. Hemodynamics, renal function, plasma renin, and aldosterone in man after 5 to 14 days of bedrest. Aviat Space Environ Med. 1975 Aug;46(8):1049–1055. [PubMed] [Google Scholar]
  43. Mullins C. B., Leshin S. J., Mierzwiak D. S., Alsobrook H. D., Mitchell J. H. Changes in left ventricular function produced by the injection of contrast media. Am Heart J. 1972 Mar;83(3):373–381. doi: 10.1016/0002-8703(72)90439-5. [DOI] [PubMed] [Google Scholar]
  44. NEWMAN E. V., MERRELL M., GENECIN A., MONGE C., MILNOR W. R., McKEEVER W. P. The dye dilution method for describing the central circulation. An analysis of factors shaping the time-concentration curves. Circulation. 1951 Nov;4(5):735–746. doi: 10.1161/01.cir.4.5.735. [DOI] [PubMed] [Google Scholar]
  45. Parker J. O., Chiong M. A., West R. O., Case R. B. Sequential alterations in myocardial lactate metaboli, S-T segments, and left ventricular function during angina induced by atrial pacing. Circulation. 1969 Jul;40(1):113–131. doi: 10.1161/01.cir.40.1.113. [DOI] [PubMed] [Google Scholar]
  46. Perrett A. D., Rowe A. S., Shahmanesh M., Allison S. P., Hartog M. Blood lipids in treated diabetics. Diabetologia. 1974 Apr;10(2):115–118. doi: 10.1007/BF01219666. [DOI] [PubMed] [Google Scholar]
  47. ROSS J., Jr, BRAUNWALD E. THE STUDY OF LEFT VENTRICULAR FUNCTION IN MAN BY INCREASING RESISTANCE TO VENTRICULAR EJECTION WITH ANGIOTENSIN. Circulation. 1964 May;29:739–749. doi: 10.1161/01.cir.29.5.739. [DOI] [PubMed] [Google Scholar]
  48. Regan T. J., Khan M. I., Ettinger P. O., Haider B., Lyons M. M., Oldewurtel H. A. Myocardial function and lipid metabolism in the chronic alcoholic animal. J Clin Invest. 1974 Sep;54(3):740–752. doi: 10.1172/JCI107812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Regan T. J., Levinson G. E., Oldewurtel H. A., Frank M. J., Weisse A. B., Moschos C. B. Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy. J Clin Invest. 1969 Feb;48(2):397–407. doi: 10.1172/JCI105997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Regan T. J., Wu C. F., Weisse A. B., Moschos C. B., Ahmed S. S., Lyons M. M. Acute myocardial infarction in toxic cardiomyopathy without coronary obstruction. Circulation. 1975 Mar;51(3):453–461. doi: 10.1161/01.cir.51.3.453. [DOI] [PubMed] [Google Scholar]
  51. Roberts W. C. Coronary arteries in fatal acute myocardial infarction. Circulation. 1972 Jan;45(1):215–230. doi: 10.1161/01.cir.45.1.215. [DOI] [PubMed] [Google Scholar]
  52. Rubler S., Dlugash J., Yuceoglu Y. Z., Kumral T., Branwood A. W., Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972 Nov 8;30(6):595–602. doi: 10.1016/0002-9149(72)90595-4. [DOI] [PubMed] [Google Scholar]
  53. SCHWARTZ C. J., MITCHELL J. R. The relation between myocardial lesions and coronary artery disease. I. An unselected necropsy study. Br Heart J. 1962 Nov;24:761–786. doi: 10.1136/hrt.24.6.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. SONES F. M., Jr, SHIREY E. K. Cine coronary arteriography. Mod Concepts Cardiovasc Dis. 1962 Jul;31:735–738. [PubMed] [Google Scholar]
  55. Sohar E., Ravid M., Ben-Shaul Y., Reshef T., Gafni J. Diabetic fibrillosis. A report of three cases. Am J Med. 1970 Jul;49(1):64–69. doi: 10.1016/s0002-9343(70)80114-0. [DOI] [PubMed] [Google Scholar]
  56. Spodick D. H., Pigott V. M., Chirife R. Preclinical cardiac malfunction in chronic alcoholism. Comparison with matched normal controls and with alcoholic cardiomyopathy. N Engl J Med. 1972 Oct 5;287(14):677–680. doi: 10.1056/NEJM197210052871401. [DOI] [PubMed] [Google Scholar]
  57. TAYLOR H. L., HENSCHEL A. Effects of bed rest on cardiovascular function and work performance. J Appl Physiol. 1949 Nov;2(5):223–239. doi: 10.1152/jappl.1949.2.5.223. [DOI] [PubMed] [Google Scholar]
  58. Vihert A. M., Zhdanov V. S., Matova E. E. Atherosclerosis of the aorta and coronary vessels of the heart in cases of various diseases. J Atheroscler Res. 1969 Mar-Apr;9(2):179–192. doi: 10.1016/s0368-1319(69)80053-0. [DOI] [PubMed] [Google Scholar]

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